Wednesday, December 1, 2010

Elevated fat and cholesterol levels found in a typical American-style diet plays an important role in the growth and spread of prostate cancer, say researchers at Thomas Jefferson University’s Kimmel Cancer Center.

Their study, the first to show such an association, is published in the December issue of The American Journal of Pathology. It demonstrates how mice eating a Western diet, and predisposed to develop prostate cancer, can develop larger tumors that are faster growing and metastasize more easily to the lungs, compared to animals eating a control diet.

In this study, a research team led by Philippe G. Frank, Ph.D., assistant professor in the Department of Stem Cell Biology and Regenerative Medicine at Jefferson, tried to understand why prostate cancer incidence is low in Asian countries, but significantly increases in Asian men who move to the United States. “Our hypothesis is that environmental factors, most likely present in the diet, may act as late stage promoters, responsible for the transformation of a prostate tumor from an early stage form into a more aggressive and clinically-apparent form,” says Dr. Frank.

Dietary fat and cholesterol have been shown to be risk factors in the development and progression of other tumor types, but diet-based studies in prostate cancer patients have reached contradictory conclusions, Dr. Frank says. For this reason, he and his colleagues turned to the TRAMP transgenic mouse model to determine the role of dietary fat and cholesterol. This mouse model is believed to closely parallel the pathogenesis of human prostate cancer.

TRAMP mice were placed on a diet that contained 21.2 percent fat and 0.2 percent cholesterol, reflective of a typical Western diet. A control group of TRAMP mice was fed a normal chow that had 4.5 percent fat and negligible amounts of cholesterol.

They found that the Western diet accelerated prostate tumor development and progression. These tumors also produced increased levels of receptors that bind to lipoproteins carriers of cholesterol, and they were more aggressive. The researchers further discovered that the TRAMP mice fed a Western diet appeared to experience greater incidence of cancer metastasis to the lungs, compared to the control group.

The research team also noted that TRAMP mice fed the high fat/high cholesterol chow had less cholesterol in their blood compared to control mice fed the same diet. “This likely reflects the fact that their tumors depend on cholesterol to grow,” explains Dr. Frank. “This study suggests that monitoring cholesterol levels in men at risk, diagnosed, or treated for prostate cancer may help limit cancer growth or even recurrence.”

Dr. Frank says the evidence involving cholesterol is strong – a finding he believes makes sense physiologically. “Cells need cholesterol to produce androgen hormones, and androgen hormones promote prostate cancer growth,” he explains. “Perhaps more importantly, we also believe that tumors feed on cholesterol, and the more blood cholesterol is accessible, the more is available for tumor growth.

“Although this is a mouse study, numerous studies have shown the health benefits of controlling blood cholesterol levels and fat intake. This research suggests the same advice may offer some benefit for men at risk of developing prostate cancer or even diagnosed with prostate cancer,” says Dr. Frank.

He adds statins that lower cellular cholesterol production may be one way to reduce prostate cancer progression – although that has yet to be demonstrated. Monitoring blood cholesterol levels of prostate cancer patients may also provide important information about cancer progression. “For example, tests showing a sudden drop in blood cholesterol is often indicative of the development of tumors,” Dr. Frank adds.